Chromone derivatives as matrix metalloproteinase inhibitors

Abstract

This invention provides compounds defined by Formula I or a pharmaceutically acceptable salt thereof,wherein R1, Q, Y2, Y3, Y4, U5, U6, U8, and R2 are as defined in the specification. The invention also provides pharmaceutical compositions comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, as defined in the specification, together with a pharmaceutically acceptable carrier, diluent, or excipient. The invention also provides methods of inhibiting an MMP-13 enzyme in an animal, comprising administering to the animal a compound of Formula I, or a pharmaceutically acceptable salt thereof. The invention also provides methods of treating a disease mediated by an MMP-13 enzyme in a patient, comprising administering to the patient a compound of Formula I, or a pharmaceutically acceptable salt thereof, either alone or in a pharmaceutical composition. The invention also provides methods of treating diseases such as heart disease, multiple sclerosis, osteo- and rheumatoid arthritis, arthritis other than osteo- or rheumatoid arthritis, cardiac insufficiency, inflammatory bowel disease, heart failure, age-related macular degeneration, chronic obstructive pulmonary disease, asthma, periodontal diseases, psoriasis, atherosclerosis, and osteoporosis in a patient, comprising administering to the patient a compound of Formula I, or a pharmaceutically acceptable salt thereof, either alone or in a pharmaceutical composition. The invention also provides combinations, comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, together with another pharmaceutically active component as described in the specification.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims benefit of priority from U.S. Provisional Patent Application No. 60 / 403,094, filed Aug. 13, 2002.FIELD OF THE INVENTION[0002]This invention relates to chromone derivatives which inhibit matrix metalloproteinase enzymes and thus are useful for treating diseases resulting from MMP-mediated tissue breakdown such as heart disease, cardiac insufficiency, inflammatory bowel disease, multiple sclerosis, osteo- and rheumatoid arthritis, arthritis other than osteo- or rheumatoid arthritis, heart failure, age-related macular degeneration, chronic obstructive pulmonary disease, asthma, periodontal diseases, psoriasis, atherosclerosis, and osteoporosis.BACKGROUND OF THE INVENTION[0003]Matrix metalloproteinases (sometimes referred to as MMPs) are naturally occurring enzymes found in most mammals. Over-expression and activation of MMPs, or an imbalance between MMPs and inhibitors of MMPs, have been suggested as factors in the pa...

AI Technical Summary

Benefits of technology

"This patent describes a new group of compounds called chromone derived compounds that have various uses. These compounds can be used as medicines, as well as in other fields such as electronics and sensors. The patent also describes different types of chromone compounds that can be made using different methods. Overall, this patent provides a new way to create and use new compounds for various applications."

Problems solved by technology

A major limitation on the use of currently known MMP inhibitors is their lack of specificity for any particular enzyme.

However, no selective or nonselective inhibitor of MMP-13 has been approved and marketed for the treatment of any disease in any mammal.

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